TRAP1 regulates autophagy in lung cancer cells.
Expression of TRAP1, a member of the HSP90 chaperone family, has been implicated in tumour protective effects, based on its differential mitochondrial localization and function. This work was designed to provide new insights into the pathways involved in TRAP1-provided cytoprotection on NSCLC. For this, TRAP1-depleted A549 human NSCLC cells and MRC-5 normal lung fibroblasts were produced using a siRNA approach and main cellular quality control mechanisms were investigated. TRAP1-depleted A549 cells displayed decreased cell viability likely due to impaired mitochondrial function including decreased ATP/AMP ratio, oxygen consumption and membrane potential, as well as increased apoptotic indicators. Furthermore, the negative impact of TRAP1 depletion on mitochondrial function was not observed in normal MRC-5 lung cells, which might be due to the differential intracellular localization of the chaperone in tumour versus normal cells. Additionally, A549 TRAP1-depleted cells showed increased autophagic flux. Functionally, autophagy inhibition resulted in decreased cell viability in both TRAP1-expressing and TRAP1-depleted tumour cells with minor effects on MRC-5 cells. Conversely, autophagy stimulation decreased cell viability of both A549 and MRC-5 TRAP1-expressing cells while in A549 TRAP1-depleted cells, increased autophagy augmented viability. Our results show that even though TRAP1 depletion affects both normal MRC-5 and tumour A549 cell proliferation, inhibition of autophagy per se led to a decrease in tumour cell mass, while having a reduced effect on the normal cell line. The strategy of targeting TRAP1 in NSCLC shows future potential therapeutic applications.


Electric field-induced oxygen vacancies in YBa2Cu3O7.
The microscopic doping mechanism behind the superconductor-to-insulator transition of a thin film of YBa2Cu3O7 was recently identified as due to the migration of O atoms from the CuO chains of the film. Here, we employ density-functional theory calculations to study the evolution of the electronic structure of a slab of YBa2Cu3O7 in the presence of oxygen vacancies under the influence of an external electric field. We find that, under massive electric fields, isolated O atoms are pulled out of the surface consisting of CuO chains. As vacancies accumulate at the surface, a configuration with vacancies located in the chains inside the slab becomes energetically preferred, thus providing a driving force for O migration toward the surface. Regardless of the defect configuration studied, the electric field is always fully screened near the surface, thus negligibly affecting diffusion barriers across the film.


Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response.
Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis by degrading misfolded proteins, inhibiting translation, and increasing expression of chaperones that enhance ER protein folding capacity. Although ER stress and protein aggregation have been implicated in aging, the role of UPR signaling in regulating lifespan remains unknown. Here we show that deletion of several UPR target genes significantly increases replicative lifespan in yeast. This extended lifespan depends on a functional ER stress sensor protein, Ire1p, and is associated with constitutive activation of upstream UPR signaling. We applied ribosome profiling coupled with next generation sequencing to quantitatively examine translational changes associated with increased UPR activity and identified a set of stress response factors up-regulated in the long-lived mutants. Besides known UPR targets, we uncovered up-regulation of components of the cell wall and genes involved in cell wall biogenesis that confer resistance to multiple stresses. These findings demonstrate that the UPR is an important determinant of lifespan that governs ER stress and identify a signaling network that couples stress resistance to longevity.


Respiratory Distress in Postanesthesia Care Unit: First Presentation of Coronavirus Disease 2019 in a 17-Year-Old Girl: A Case Report.
A 17-year-old healthy girl underwent an uneventful esthetic septorhinoplasty. She was easily extubated and transferred to the postanesthesia care unit (PACU) with oxygen saturation (SpO2) of 96%. About 30 minutes after arrival in the PACU, she developed dyspnea with SpO2 of 84% and promptly received oxygen with bilevel positive airway pressure in conjunction with low-dose corticosteroid. The subsequent chest computed tomography (CT) revealed bilateral patchy infiltrates similar to the radiologic findings of Coronavirus Disease 2019 (COVID-19). Finally, a reverse transcriptase polymerase chain reaction (RT-PCR) of a pharyngeal specimen confirmed the diagnosis of COVID-19.


Total nucleated cell counts are driving clinician's choice rather than cryopreservation period: Lesson for cord blood banks.
According to the increase in both the number of cryopreserved cord blood (CB) units and the cryopreservation period for each CB unit in the largest public CB bank in Korea, we are pursuing greater efficiency in CB bank management. Thus, we analyzed whether the cryopreservation period has a negative impact on the selection of CB units for CB transplantation (CBT). Until December 2019, 468 CB units were used for transplantation. The cryopreservation period, total nucleated cell (TNC), and CD34+ cell counts were analyzed among the CB units according to the CBT-year and the donation year. The results showed that the cryopreservation period was increased in recent CBT-year groups. The transplanted CB units showed similar TNC counts irrespective of the donation year, and the mean TNC count was 13.9 × 108/unit. CB units cryopreserved for a relatively long period were transplanted consistently. The mean TNC count of CB units cryopreserved for over 10 years was 16.4 × 108/unit. The mean CD34+ cell counts were not significantly different among the CB units transplanted after CBT-2013 and among the CB units donated after CBT-2011. Through an analysis of the CB units selected by clinicians for CBT, this study revealed that clinicians placed more weight on the TNC counts than on the cryopreservation period of cryopreserved CB units. Therefore, the minimum TNC count of CB units suitable for cryopreservation should be increased up to 13.0 × 108/unit to balance the satisfaction of clinicians' needs with the efficiency of the CB bank.


Endoscopic retrograde cholangio-pancreatography in dogs with chronic gastrointestinal problems.
Endoscopic retrograde cholangio-pancreatography is a combination of endoscopy and fluoroscopy used for radiographic imaging of the biliary and pancreatic ducts. In order to assess its feasibility and to describe abnormal findings in dogs, this technique was performed in 30 dogs with nonspecific chronic gastrointestinal disturbances. Using an 11-mm side-view endoscope, retrograde cholangiography was successful in 20/30 dogs (67%) and pancreatography in 21/30 (70%). Success was affected by intraduodenal food, mucus or blood, problems in papillary cannulation, stomach overdistention, body size, and changes in duodenal mucosa. It was impossible to perform the procedure in dogs weighing < 10 kg with the available material. Endoscopic retrograde cholangiography revealed findings that differed from previous reports in healthy beagles in 5/20 dogs. Findings included enlarged common bile duct (n = 2), intraductal filling defects (n = 2), and deviated course of common bile duct (n = 1), and major papilla stenosis (n = 1). In the dog with major papilla stenosis and intraductal filling defects, endoscopic guided sphincterotomy was performed. Endoscopic retrograde pancreatography revealed an abnormal course of the accessory pancreatic duct in 2/21 dogs. In both dogs with proven end-stage pancreatic acinar atrophy, the left duct branch did not run distal the stomach to the left but went parallel to the right duct branch and the duodenum. Repeated clinical and laboratory examinations revealed no signs of complications after endoscopic retrograde cholangio-pancreatography. It was concluded that this imaging technique is promising for the diagnosis of biliary and pancreatic diseases in dogs. It also offers the chance for new treatment options such as endoscopic guided sphincterotomy in dogs.


Thermotolerance and radiation sensitizing effects of long duration, mild temperature hyperthermia.
Clinical application of long duration hyperthermia at temperatures < 42 degrees C has traditionally been avoided because of the possibility of chronic thermotolerance development, such as is observed with rodent cells. In support of long duration hyperthermia, both rodent and human cells have been shown to be sensitized to low dose-rate irradiation by simultaneous heating at 40 or 41 degrees C. The relationship between these supposed contradictory responses to hyperthermia were investigated in rat 9L gliosarcoma cells in vitro. Thermotolerance developed during 41 degrees C heating with or without concurrent low dose-rate irradiation. Thermotolerance reached a maximum within 6 h during 41 degrees C heating and remained stable for at least 24 h. When cells were returned to 37 degrees C after heating at 41 degrees C for 6 h, thermotolerance remained stable for at least 12 h. The time course of thermotolerance development correlated with that of induction of 41 degrees C radiation sensitization. Radiation sensitization, on the other hand, was shown to be independent of thermotolerance because the protein synthesis inhibitor cycloheximide prevented thermotolerance induction but had no effect on radiation sensitization. We conclude that thermotolerance development during concurrent clinical application of long duration mild temperature hyperthermia and low dose-rate irradiation should not be a factor in altering treatment outcome.


Integrated and efficient diffusion-relaxometry using ZEBRA.
The emergence of multiparametric diffusion models combining diffusion and relaxometry measurements provides powerful new ways to explore tissue microstructure, with the potential to provide new insights into tissue structure and function. However, their ability to provide rich analyses and the potential for clinical translation critically depends on the availability of efficient, integrated, multi-dimensional acquisitions. We propose a fully integrated sequence simultaneously sampling the acquisition parameter spaces required for T1 and T2* relaxometry and diffusion MRI. Slice-level interleaved diffusion encoding, multiple spin/gradient echoes and slice-shuffling are combined for higher efficiency, sampling flexibility and enhanced internal consistency. In-vivo data was successfully acquired on healthy adult brains. Obtained parametric maps as well as clustering results demonstrate the potential of the technique to provide eloquent data with an acceleration of roughly 20 compared to conventionally used approaches. The proposed integrated acquisition, which we call ZEBRA, offers significant acceleration and flexibility compared to existing diffusion-relaxometry studies, and thus facilitates wider use of these techniques both for research-driven and clinical applications.


Manual aspiration thrombectomy using a Penumbra catheter in patients with acute migrated MCA occlusion.
Background We retrospectively assessed the efficacy and safety of manual aspiration thrombectomy (MAT) using a Penumbra catheter in patients with acute migrated middle cerebral artery (MCA) occlusion. Methods We conducted a retrospective review of patients who underwent MAT using Penumbra 4 or 5 MAX reperfusion catheters for the treatment of acute MCA occlusion between January 2012 and December 2015. A migrated thrombus was defined as distal migration greater than ≥1 cm on initial cerebral angiography compared with preprocedural angiographic findings. We evaluated immediate angiographic results and clinical outcomes through a review of electronic medical records and compared clinical outcomes between migrated and non-migrated MCA occlusions. Results During this period, 98 patients underwent MAT using Penumbra catheters for treatment of acute MCA occlusions. Of these, 19 (19.4%) had a migrated MCA thrombus on initial cerebral angiography compared with preprocedural angiographic findings. The overall rate of successful recanalization (TICI grade ≥ 2b) was 90.8%. The rate of successful recanalization in the migrated thrombus group was 94.7% (18/19). Overall procedure time for recanalization in the migrated thrombus group was significantly shorter than that in the non-migrated thrombus group ( p = 0.001). Although the difference was not significant, there was a trend toward more favorable clinical outcomes in the migrated thrombus group compared to the non-migrated thrombus groups (78.9% versus 60.8%, p = 0.231). Conclusion MAT appears to be safe and can achieve a high rate of successful recanalization and favorable clinical outcomes with short procedure time and without serious complications in patients with acute migrated MCA occlusion.


The Role of Protein Restriction in the Progression of Chronic Kidney Disease.
Even though nephrology has made much progress, reducing the progression of the chronic kidney disease remains, in fact, one of the biggest challenges. Long before the renal replacement therapy (RRT), it was known that limiting the protein could help almost all uremia symptoms. Although it was proposed as early as the 1960s, it only became widely used in the 1980s. By lowering the urea and other nitrogen wastes and lowering the metabolic acidosis, oxidative stress, and insulin resistance, limiting the amount of protein in your diet can help improve uremic symptoms. Also, limiting the protein in the diet positively controls the cardiovascular complications, including the arterial blood pressure and proteinuria reduction, which are risk factors for CKD progression. This mini-review examines the impact of protein restriction on the possibility of slowing CKD progression in depth.


Starch accumulation in hulless barley during grain filling.
Starch consists of two types of molecules: amylose and amylopectin. The objective of this study was increase understanding about mechanisms related to starch accumulation in hulless barley (Hordeum vulgare L.) grain by measuring temporal changes in (i) grain amylose and amylopectin content, (ii) starch synthase activity, and (iii) the relative expressions of key starch-related genes. The amylopectin/amylose ratio gradually declined in both Beiqing 6 and Kunlun 12. In both cultivars, the activities of adenosine diphosphate glucose pyrophosphorylase, soluble starch synthase (SSS), granule bound starch synthase (GBSS), and starch branching enzyme (SBE) increased steadily during grain filling, reaching their maximums 20-25 days after anthesis. The activities of SSS and SBE were greater in Ganken 5 than in either Beiqing 6 or Kunlun 12. The expression of GBSS I was greater in Beiqing 6 and Kunlun 12 than in Ganken 5. In contrast, the expression of SSS I, SSS II and SBE I was greater in Ganken 5 than in Beiqing 6 and Kunlun 12. The peak in GBSS I expression was later than that of SSS I, SSS II, SBE IIa and SBE IIb. The GBSS I transcript in Kunlun 12 was expressed on average 90 times more than the GBSS II transcript. The results suggest that SBE and SSS may control starch synthesis at the transcriptional level, whereas GBSS I may control starch synthesis at the post transcriptional level. GBSS I is mainly responsible for amylose synthesis whereas SSS I and SBE II are mainly responsible for amylopectin synthesis in amyloplasts.


Impaired microglia fractalkine signaling affects stress reaction and coping style in mice.
Microglia, resident immune cells of the CNS are sensitive to various perturbations of the environment, such as stress exposure, and may be involved in translating these changes to behavior. Among the pathways mediating stress-related neuronal cues to microglia, the fractalkine-fractalkine receptor (CX3CR1) signaling plays a crucial role. Using mice, in which the CX3CR1 gene was deleted, we explored hormonal and behavioral responses to acute and chronic stress along with changes in hypothalamic microglia. CX3CR1-/- animals display active escape in forced swim- and tail suspension tests, exaggerated neuronal activation in the hypothalamic paraventricular nucleus and increased corticosterone release in response to restraint. Analysis of Iba1 immunostaining of hypothalamic sections revealed stress-related reduction of microglia in CX3CR1-/- mice. Because microglia also contribute to energy balance regulation, we characterized metabolic phenotype of CX3CR1-/- mice. Comparison of respiratory exchange ratio did not show genotype effect on fuel preference, however, the energy expenditure was increased in CX3CR1-/- mice, which may be related to their active coping behavior. Microglia and fractalkine signaling has been repeatedly shown to be involved chronic stress-induced depressive state. CX3CR1-/- mice did not become anhedonic in the "two hit" chronic stress paradigm, confirming resistance of these animals to chronic stress-induced mood alterations. However, there was no difference in stress hormone levels, open field performance and hypothalamic microglia distribution between the genotypes. These results highlight differential involvement of microglia fractalkine signaling in controlling/integrating hormonal-, metabolic and behavioral responses to acute and chronic stress challenges.


Effects of UV Radiation on Photosynthesis, Antioxidant Capacity and the Accumulation of Bioactive Compounds in Gracilariopsis longissima, Hydropuntia cornea and Halopithys incurva (Rhodophyta).
The red macroalgae Hydropuntia cornea, Gracilariopsis longissima and Halopithys incurva were cultured for 14 d under laboratory conditions, in enriched seawater with a high nutrient content (N-NH4+ and P-PO43- ) and two radiation regimes: PAR (400-700 nm) and PAB (280-700 nm). The UV radiation effects under high availability of nutrients on growth, photosynthetic pigments (chlorophyll a, carotenoids and phycobiliproteins), photosynthetic activity and biochemical composition were studied. Maximum quantum yield (Fv /Fm ) was not significantly different among the PAR and PAB treatments during the experiment. However, the maximum electronic transport rate (ETRmax ) increased over time, showing the highest values in PAR for H. incurva and H. cornea, whereas for G. longissima it was found in PAB. Photosynthetic efficiency (αETR ) decreased over time in the first two species, but increased in G. longissima. Saturation irradiance (EkETR ) and maximum nonphotochemical quenching (NPQmax ) increased in PAB with time up to 80% and 30%, respectively, indicating a photosynthetic acclimatization like that of sun-type algae. Five MAAs were identified in all species using high performance liquid chromatography (HPLC). The total content of MAAs increased over time, being 30% higher in H. incurva, 40% in G. longissima and 50% in H. cornea in PAB than in the PAR treatment. Finally, the antioxidant activity was also higher in the PAB treatment. All of the species presented an effective mechanism of photoprotection based on the accumulation of photoprotective compounds with antioxidant activity, as well as a high dissipation of excitation energy (high NPQmax ).


Emerging antibodies for the treatment of pancreatic cancer.
Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.


Effect of Intravenous Infusion of G-CSF-Mobilized Peripheral Blood Mononuclear Cells on Upper Extremity Function in Cerebral Palsy Children.
To investigate the effect of intravenous infusion of peripheral blood mononuclear cells (mPBMC) mobilized by granulocyte-colony stimulating factor (G-CSF) on upper extremity function in children with cerebral palsy (CP). Fifty-seven children with CP were enrolled. Ten patients were excluded due to follow-up loss. In total, 47 patients (30 males and 17 females) were analyzed. All patients' parents provided signed consent before the start of the study. After administration of G-CSF for 5 days, mPBMC was collected and cryopreserved. Patients were randomized into two groups 1 month later. Twenty-two patients were administered mPBMC and 25 patients received normal saline as placebo. Six months later, the two groups were switched, and administered mPBMC and placebo, respectively. Quality of Upper Extremity Skills Test (QUEST) and the Manual Ability Classification System (MACS) were used to evaluate upper motor function. All subdomain and total scores of QUEST were significantly improved after mPBMC and placebo infusion, without significant differences between mPBMC and placebo groups. A month after G-CSF, all subdomain and total scores of QUEST were improved. The level of MACS remained unchanged in both mPBMC and placebo groups. In this study, intravenously infused mPBMC showed no significant effect on upper extremity function in children with CP, as compared to placebo. The effect of mPBMC was likely masked by the effect of G-CSF, which was used in both groups and/or G-CSF itself might have other neurotrophic potentials in children with CP.


Identification of RIP-II toxins by affinity enrichment, enzymatic digestion and LC-MS.
Type 2 ribosome-inactivating protein toxins (RIP-II toxins) were enriched and purified prior to enzymatic digestion and LC-MS analysis. The enrichment of the RIP-II family of plant proteins, such as ricin, abrin, viscumin, and volkensin was based on their affinity for galactosyl moieties. A macroporous chromatographic material was modified with a galactose-terminated substituent and packed into miniaturized columns that were used in a chromatographic system to achieve up to 1000-fold toxin enrichment. The galactose affinity of the RIP-II proteins enabled their selective enrichment from water, beverages, and extracts of powder and wipe samples. The enriched fractions were digested with trypsin and RIP-II peptides were identified based on accurate mass LC-MS data. Their identities were unambiguously confirmed by LC-MS/MS product ion scans of peptides unique to each of the toxins. The LC-MS detection limit achieved for ricin target peptides was 10 amol and the corresponding detection limit for the full method was 10 fmol/mL (0.6 ng/mL). The affinity enrichment method was applied to samples from a forensic investigation into a case involving the illegal production of ricin and abrin toxins.


Data from mass spectrometry, NMR spectra, GC-MS of fatty acid esters produced by Lasiodiplodia theobromae.
The data described herein is related to the article with the title "Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings" C.C. Uranga, J. Beld, A. Mrse, I. Cordova-Guerrero, M.D. Burkart, R. Hernandez-Martinez (2016) [1]. Data includes nuclear magnetic resonance spectroscopy and GC-MS data used for the identification and characterization of fatty acid esters produced by L. theobromae. GC-MS traces are also shown for incubations in defined substrate, consisting in Vogel׳s salts supplemented with either 5% grapeseed oil or 5% glucose, the two combined, or 5% fructose. Traces for incubations in the combination of 5% grapeseed oil and 5% glucose for different fungal species are also included. Images of mycelium morphology when grown in 5% glucose with or without 5% grapeseed oil are shown due to the stark difference in mycelial pigmentation in the presence of triglycerides. High concentration gradient data for the plant model Nicotiana tabacum germinated in ethyl stearate (SAEE) and ethyl linoleate (LAEE) is included to show the transition between growth inhibition and growth induction in N. tabacum by these compounds.


Dietary diversity score is related to obesity and abdominal adiposity among Iranian female youth.
To assess the relationship between diet and disease, consideration of whole-diet indices may be more informative than single-nutrient intake. The present study was conducted to report the relationship among dietary diversity score (DDS), obesity and abdominal adiposity among female university students. Cross-sectional study. Isfahan, Iran. A representative sample of 289 healthy female students aged 18-28 years was selected randomly from Isfahan University of Medical Sciences, Iran. Usual dietary intake was assessed using a validated semi-quantitative FFQ. DDS was calculated according to the scoring of the five food groups based on the US Department of Agriculture Food Guide Pyramid. This is a score of diet variety, and shows the diversity of the consumed diet. Participants were categorised on the basis of quartile cut-off points of DDS. Potential confounders such as age, total energy intake and physical activity were considered in all the analyses. The means (sd) of BMI and waist circumference were 25.9 (sd 5.1) kg/m2 and 85·5 (sd 14) cm, respectively. The probability of obesity decreased with quartiles of DDS (OR among quartiles: 1.00, 0.41, 0.31 and 0.21, P = 0.03; this was the same for abdominal adiposity: 1.00, 0.55, 0.36 and 0.21, P = 0.02). Those in the lowest quartile of the DDS had the highest risk for being overweight. There were inverse associations among DDS, obesity and abdominal adiposity among the female students of Isfahan University. Further prospective investigations are needed to confirm this finding.


Infrared laser desorption/ionization on silicon.
Laser desorption/ionization from a single-crystal silicon surface was performed using a laser operating in the 3-microm region of the mid-infrared. Analyte molecules up to 6 kDa were ionized with no added matrix. As with ultraviolet desorption/ionization from porous silicon (DIOS), IR laser desorption from silicon does not produce matrix ions that can interfere with analysis of low-mass analytes. However, in contrast to UV DIOS, silicon porosity or roughness is not required for ionization using an IR laser. Mass spectra were obtained in the wavelength range between 2.8 and 3.5 microm, which is consistent with energy absorption by a hydrogen-bonded OH group. A mechanism based on desorption of adsorbed solvent molecules is postulated.


Inorganic and methylated arsenic compounds induce cell death in murine macrophages via different mechanisms.
We demonstrate in this study the cytotoxic effects of inorganic arsenicals, arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid (MAA), dimethylarsinic acid (DMAA), and trimethylarsine oxide (TMAO), which are metabolites of inorganic arsenicals in human bodies, using murine macrophages in vitro. Inorganic arsenicals, both arsenite and arsenate, are strongly toxic to macrophages, and the concentration that decreased the number of surviving cells to 50% of that in untreated controls (IC50) was 5 or 500 microM, respectively. These inorganic arsenicals mainly caused necrotic cell death with partially apoptotic cell death; about 80% of dead cells were necrotic, and 20% were apoptotic. The inorganic arsenicals also induced marked release of an inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), at cytotoxic doses. This strong cytotoxicity of an inorganic arsenical, arsenite, might be mediated via active oxygen and protease activation because it was inhibited by the addition of some antioxidant reagents, such as superoxide dismutase (SOD), catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting enzyme (ICE). It is likely that these immunotoxic effects of inorganic arsenicals may evoke both immunosuppression and inflammation, and they may be central factors causing carcinogenesis and severe inflammatory responses, such as hepatomegaly and splenomegaly, in chronic arsenicosis patients who daily ingested arsenic-contaminated well water. In contrast, the cytotoxic effects of methylated arsenic compounds were lower than those of inorganic arsenicals. The IC50 value of DMAA was about 5 mM, and MAA and TMAO had no toxicity even at concentrations over 10 mM. Additionally, these methylated chemicals suppressed the TNFalpha release from macrophages. DMAA induced mainly apoptotic cell death in macrophages as indicated by cellular morphological changes, condensed nuclei, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and DNA fragmentation. However, the cytotoxicity of DMAA might be induced via a different mechanism from that of inorganic arsenicals because it was not abolished by the additions of SOD, catalase, or ICE inhibitor. Conversely, GSH enhanced the toxicity of DMAA. These data suggest that methylation of inorganic arsenicals in mammals plays an important role in suppression of both severe immunosuppression and inflammatory responses caused by inorganic arsenicals.


[Rhabdoid tumors of the kidney in childhood].
The primary diagnosis of renal masses in children is made by imaging studies. This retrospective analysis describes the imaging features of rhabdoid tumors (RT) with US, CT and MRI, to point out characteristics and to evaluate the possibility of differentiation between RT and Wilms tumor. We reviewed 10 MRI (6 STIR, 9 T1 w, 8 T2 w, 10 T1 post KM), 15 CT (9 Nativ-CT, 14 KM-CT) and 14 US images of 22 patients (age 2 - 57 months) with histopathologically confirmed RT. The following characteristics were evaluated: subcapsular fluid collection, multiple tumor lobules, presence of calcification, primary tumor size, visibility of tumor margin, tumor necrosis and metastases. The mean total tumor volume was 238 ml. 19 RT were located in the perihilar/medullary region with invasion of the renal hilum, and 5/22 tumors showed multiple tumor lobules. Subcapsular fluid collection was found in 6/22 cases. Calcifications were present in 6/19. Eleven tumors were well defined from the renal parenchyma, 9 poorly defined, 2 could not be assessed. In 19/22 cases tumor necrosis was found. Distant metastases were seen in 8 cases in the lung, in 3 cases in the CNS. Metastases of regional lymph nodes were seen in 9 cases. The evaluated characteristics frequently found in RT are not indicative of these tumors. RT cannot clearly be differentiated from Wilms tumor by imaging studies. Because of frequent involvement of the CNS and lung, a MRI of the CNS and CT of the lung is indicated after histopathologic diagnosis of RT is made.


[Anesthetic Management of a Patient with Central Core Disease for Scoliosis Surgery].
Central core disease (CCD) is a dominantly inherited congenital myopathy. CCD is also associated with muscular and skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities. CCD and malignant hyperthermia (MH) are both associated with mutations in the ryanodine receptor on chromosome 19q13.1. An 11-year-old boy with CCD complicated with severe scoliosis was scheduled for spinal fusion surgery under general anesthesia. Furthermore, he had trismus caused by temporomandibular contracture. He was considered as MH susceptible. Anesthesia was managed with remifentanil and propofol without using muscle relaxtants and volatile anesthetics. We could intubate the trachea with Airtraq laryngoscope without any complications. The perioperative course was uneventful.


Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary-Gonadal Axis Activation in Fetal and Neonatal Life.
Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.


A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes.
We characterized serum from a patient with polymyositis, and found that it produced a peripheral (rim) fluorescent antinuclear antibody pattern on rat liver substrate. Indirect immunofluorescence analysis revealed a punctate pattern at the nuclear surface of PtK2, BHK-21, and HEp-2 cells. This pattern was still present after sequential extraction in situ with non-ionic detergent, DNase, RNase, and high ionic strength buffer (2M NaCl). Immunogold electron microscopic localization was specific for nuclear pore complexes. By immunoblot analysis, the antigens were polypeptides of 200 kd and 130 kd that were enriched in the nuclear fraction.


Effects of Trimetazidine on PDCD4/NF-κB/TNF-α Pathway in Coronary Microembolization.
The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs. 20 Bama mini pigs were randomized into sham operation (sham), microembolization (CME), TMZ, and siRNA-PDCD4 groups (n = 5). The CME model was established by injecting polyethylene microspheres via microcatheter into the left anterior descending coronary artery. The TMZ group was injected 2.5 mg/kg drug via ear vein 30 min before CME; whereas, the siRNA-PDCD4 group was transfected with PDCD4 siRNA at the left anterior descending coronary artery via microcatheter 72h before CME. Cardiac function indexes were measured using cardiac echocardiography. The mRNA expression of PDCD4 and TNF-α in the myocardium was detected by quantitative fluorescence PCR, and the protein expression of PDCD4, NF-κB (p65), and TNF-α by Western blot. Echocardiographic parameters showed lower cardiac function and higher serum cTnI level in the CME group than sham, which was manifested as reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), cardiac output (CO), and increased left ventricular diastolic diameter (LVEDd). Compared to the CME group, the CME-induced cardiac function injury was reduced, and the serum cTnI level was decreased in the TMZ and siRNA-PDCD4 groups. The expressions of PDCD4, NF-κB (p65), and TNF-α were significantly increased in the CME than the sham groups (P < 0.05), and significantly decreased in the TMZ and siRNA-PDCD4 groups than the CME group (P < 0.05). TMZ pretreatment effectively reduced the myocardial damage caused by CME via inhibiting the PDCD4/NF-κB/ TNF-α pathway in cardiomyocytes.


Identification of Risk Areas for Intestinal Schistosomiasis, Based on Malacological and Environmental Data and on Reported Human Cases.
The aim of the present study was to use an integrated approach for the identification of risk areas for Schistosoma mansoni transmission in an area of low endemicity in Minas Gerais, Brazil. For that, areas of distribution of Biomphalaria glabrata were identified and were related to environmental variables and communities with reported schistosomiasis cases, in order to determine the risk of infection by spatial analyses with predictive models. The research was carried out in the municipality of Alvorada de Minas, with data obtained between the years 2017 and 2019 inclusive. The Google Earth Engine was used to obtain geo-climatic variables (temperature, precipitation, vegetation index and digital elevation model), R software to determine Pearson's correlation and MaxEnt software to obtain an ecological model. ArcGis Software was used to create maps with data spatialization and risk maps, using buffer models (diameters: 500, 1,000 and 1,500 m) and CoKriging. Throughout the municipality, 46 collection points were evaluated. Of these, 14 presented snails of the genus Biomphalaria. Molecular analyses identified the presence of different species of Biomphalaria, including B. glabrata. None of the snails eliminated S. mansoni cercariae. The distribution of B. glabrata was more abundant in areas of natural vegetation (forest and cerrado) and, for spatial analysis (Buffer), the main risk areas were identified especially in the main urban area and toward the northern and eastern extensions of the municipality. The distribution of snails correlated with temperature and precipitation, with the latter being the main variable for the ecological model. In addition, the integration of data from malacological surveys, environmental characterization, fecal contamination, and data from communities with confirmed human cases, revealed areas of potential risk for infection in the northern and eastern regions of the municipality. In the present study, information was integrated on epidemiological aspects, transmission and risk areas for schistosomiasis in a small, rural municipality with low endemicity. Such integrated methods have been proposed as important tools for the creation of schistosomiasis transmission risk maps, serve as an example for other communities and can be used for control actions by local health authorities, e.g., indicate priority sectors for sanitation measures.


Effectiveness of lifestyle modification on quality of life among uncontrolled diabetics and hypertensives in India - Community based intervention study.
Diabetes and hypertension contribute to more than half of morbidity, mortality and years lived with disability in developing countries like India. It impacts the quality of life (QoL) of patients and their family. Management of these diseases is in infancy and emphasis is laid on pharmacological interventions. Though nonpharmacological measures are crucial for management, their implementation is questionable. Hence, this study was conducted to measure the effectiveness of lifestyle modifications on QoL among uncontrolled hypertensives and diabetics in rural India. An interventional study was done in 3 villages with 100 participants each, where village one received lifestyle modification as intervention and village two physical activity and village three control receiving standard care. The baseline data included socio-demographic characteristics such as awareness of hypertension, diabetes, lifestyle pattern and physical activity, and WHO QoL. The participants were trained, followed up, and assessed after 12 months following intervention. QoL scores between groups and pre- and post-intervention in the group were compared using Mann-Whitney U and Wilcoxon signed-rank test, respectively. In this study, there was a significant improvement in overall QoL and in all the four domains, namely physical, psychological, social relationship, and environmental domains in both the intervention villages. QoL was significantly better in both the intervention groups following intervention than compared to the control group. QoL improves with intervention on uncontrolled diabetics and hypertensives. It is time to emphasize on the collaboration among physicians and on the holistic integrative health services delivery for non-communicable diseases.


Attachment styles, grief responses, and the moderating role of coping strategies in parents bereaved by the Sewol ferry accident.
Background: Previous studies on the influence of different types of attachment on grief responses have yielded contradictory outcomes. Little research has been conducted to identify the psychological processes that moderate the relationship between attachment representations and patterns of grief in disaster-related grief. Objective: The present study examines the effects of different attachment types on the grief responses of parents bereaved by loss of a child in a ferry accident, along with the moderating role of coping strategies. Methods: Bereaved parents (n = 81) completed self-report questionnaires evaluating attachment, coping strategies, complicated grief, and shame/guilt. We performed correlational analyses to examine the associations among variables. We also conducted hierarchical regression analyses and simple slope analyses to examine the moderation effects of coping strategies. Results: Anxious attachment was associated with severe shame/guilt, and avoidant attachment correlated with complicated grief. Anxious attachment was positively associated with all types of coping strategies, and avoidant attachment was negatively related to problem- and emotion-focused coping. The use of problem-focused coping strategies was a significant moderator of the relationship between the avoidant attachment dimension and shame/guilt. Avoidant attachment had a significant effect on shame/guilt in groups with a high level of problem-focused coping. In contrast, none of the coping strategies significantly moderated the relationship between anxious attachment and grief response. Conclusions: The results suggest that people with highly avoidant attachment might be overwhelmed by shame and guilt when they try to use problem-focused coping strategies. This finding suggests that grief interventions should be organized with consideration of individual differences in attachment representations.


Hypoxic syncope.
Syncope at altitude of otherwise healthy individuals is a well-known phenomenon (22). We report on the cardiovascular effects observed in subjects exposed to hypoxia to illustrate the role of the sympathetic-adrenergic system in hypoxic syncope. This study describes unexpected episodes of (near) syncope during two crossover trials at simulated altitude in a low pressure chamber. In study A, 30 healthy male volunteers underwent 4 exposures to short-term (20 min) acute severe hypoxia (20,000 ft or 6096 m) to assess psychological performance. In study B, five volunteers were studied during prolonged exposure (1 h) to moderate hypoxia (13,500 ft or 4115 m) with and without concomitant low dose infusion with atrial natriuretic peptide to investigate the effects on pulmonary gas exchange. In study A (acute severe hypoxia), 6 out of 120 exposures (5%), in 5 subjects, were accompanied by lightheadedness, pallor, sweating, and bradycardia. Two subjects (2%) had syncope with cardiac asystole. In study B during moderate hypoxia without atrial natriuretic peptide, adverse reactions were absent and the (nor)epinephrine levels remained unchanged. Concomitant infusion with atrial natriuretic peptide resulted in near syncope (recumbent in 3, standing in 2) at an oxygen saturation of 82%. While the epinephrine level had eightfold increased, mean arterial pressure fell from 94 to 40 mm Hg and heart rate from 79 to 44 bpm. The norepinephrine level remained unchanged illustrating a dissociated sympathetic-adrenergic response. All subjects with syncope recovered spontaneously within few minutes in Trendelenburg's position with oxygen supplied. None suffered from prolonged side effects. It is concluded that exposure to acute severe hypoxia is a sufficient cause for syncope in healthy individuals. Enhanced vasodilatation to epinephrine may contribute to the withdrawal of sympathetic and enhancement of parasympatic activity, leading to vascular collapse, bradycardia or asystole (Bezold-Jarisch reflex). Patients fully recover in Trendelenburg's position with supplemental oxygen and further clinical examinations are not necessary.


Increased susceptibility of blood type O individuals to develop anemia in Plasmodium vivax infection.
Plasmodium vivax has been reported to cause severe malaria, and one of the main resulting complications is anemia. Considering that P. vivax infects only young erythrocytes, anemia has been associated with the destruction of infected and non-infected erythrocytes. However, few studies have focused on understanding the relationship between the pathogenesis of P. vivax malaria and human genetic polymorphisms. Although ABO groups seem to influence the outcome of Plasmodium falciparum malaria, the association between P. vivax and ABO blood groups has been minimally investigated. Thus, we investigate the correlation between ABO blood groups and anemia induced by P. vivax infection. Five single nucleotide polymorphisms at the ABO gene were genotyped by PCR-RFLP and Real-Time PCR in P. vivax-infected subjects. The ABO blood types were associated with the hematological data of the patients. Our main finding was that type O infected-individuals showed lower levels of hemoglobin and hematocrit compared to type A-infected individuals. The correlation between ABO blood groups and hemoglobin levels remained significant when a multiple linear regression was applied with the possible confounding effects of clinical-epidemiologic variables taken into account. The finding that type O individuals have a higher frequency of anemia is a first step to understand the mechanisms involved in malaria anemia, which could be associated to increased destruction of type O erythrocytes.


Simultaneous Determination and Comparative Pharmacokinetics of Fuzi Water-Soluble Alkaloids between Normal and Acute Heart Failure Rats by Ultra Performance Liquid Chromatography Method.
In order to compare the pharmacokinetics of Fuzi water-soluble alkaloids between normal and acute heart failure rats, an ultra performance liquid chromatography (UPLC) method for simultaneous determination of it in rat plasma was developed. Plasma samples were treated by protein precipitation method. Seven water-soluble alkaloids were separated on a CAPCELL column and detected under the optimized chromatography condition. The calibration curves of seven targeted components showed good linearity with r2 > 0.9990 with average recoveries from 82.72 to 103.33% and matrix effect ranged from 90.02 to 104.03%. The intra- and inter-batch relative standard deviations were <10.72%, and the relative error of accuracy was within the range of -12.79-4.44%, respectively. After oral administration, the pharmacokinetic characteristics of it were investigated. Compared with the normal group, the Cmax and AUClast (area under the plasma concentration-time curve from the time of dosing to the time of last quantifiable concentration) of seven components except 3-Methoxy-p-tyramine Hydrochloride were obviously increased with remarkable prolonged t1/2 in acute heart failure group. In conclusion, a rapid, simple and sensitive UPLC method for the simultaneous quantification of seven water-soluble alkaloids in rat plasma was developed and validated for the first time. And the study showed that the disease condition had an impact on pharmacokinetics of Fuzi water-soluble alkaloids in rats in vivo.


Photochromism of a Spiropyran in Low-Temperature Matrices: Unprecedented Bidirectional Switching between a Merocyanine and an Allene Intermediate.
Photochromism of spiropyrans has attracted much attention due to its potential in many light-controlled system applications. However, several fundamental aspects regarding the structure, energetics, and mechanistic details of the transformations of spiropyrans are still not well understood. Here, we report the study of the photochromism of a 6-hydroxy-spiropyran (HBPS) under conditions of matrix isolation, where monomers of the compound are frozen in a solidified noble gas (krypton, at 15 K). The structure of the matrix-isolated HBPS was first elucidated by infrared (IR) spectroscopy supported by density functional theory computations. Then, the photochromism of HBPS, from the colorless spiropyran to the colored merocyanine, was induced by ultraviolet (UV) irradiation at 310 nm. The analysis of the IR spectrum of the photoproduced species revealed the exclusive formation of the most stable merocyanine MC-TTC stereoisomer. Subsequent visible-light (550 nm) irradiation of MC-TTC generated a new colorless allenic isomeric species ALN, where the UV irradiation (310 nm) of ALN was found to convert this species back to MC-TTC. This constitutes an unprecedented bidirectional transformation between a colored merocyanine and a colorless allene species. The newly observed photoswitching reaction (or photochromism) occurs along an intramolecular hydrogen bond existing in both merocyanine and allenic species, thus suggesting that it might be generally feasible in the chemistry of spiropyrans. On the other hand, the usual assumption that, as a general rule, merocyanines photochemically revert to spiropyrans is not supported in this work.


Molecular modeling of human cytochrome P450-substrate interactions.
The results of homology modeling of 10 human cytochrome P450 (CYP) enzymes involved in the Phase 1 metabolism of drugs and other foreign compounds are reported. The models have been constructed from the CYP102 hemoprotein domain template for which the substrate-bound crystallographic coordinates are available. Selective substrates of individual human P450s: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP4A11 are all shown to fit within the corresponding enzymes' active sites in such a manner that is consistent with reported experimental data for both known pathways of substrate metabolism and from the results of site-directed mutagenesis, either in those particular human P450 enzymes concerned or for ones within the same subfamily. The self-consistency of these homology models indicates that they may have potential utility for the pre-screening of novel drug structures.


Sex matters: association between callous-unemotional traits and uncinate fasciculus microstructure in youths with conduct disorder.
Among youths with conduct disorder, those with callous-unemotional traits are at increased risk for persistent antisocial behaviour. Although callous-unemotional traits have been found to be associated with white-matter brain abnormalities, previous diffusion imaging studies were conducted in small samples, preventing examination of potential sex by callous-unemotional traits interaction effects on white matter. Here, we used tract-based spatial statistics at a whole-brain level and within regions of interest to compare the white matter correlates of callous-unemotional traits in female vs. male youths with conduct disorder, in a sample (n = 124) recruited through a multi-site protocol. A sex-specific association between callous-unemotional traits and white matter was found in the left uncinate fasciculus, where callous-unemotional traits were positively associated with axial diffusivity in males, while an opposite pattern was found in females. These findings are in line with previous studies suggesting that the uncinate fasciculus is a key tract implicated in the development of psychopathy, but also add to recent evidence showing that sexual dimorphism needs to be taken into account when examining the structural correlates of mental disorders in general, and callous-unemotional traits in conduct disorder in particular.


Morphology favors an endothelial cell pathway for longitudinal conduction within arterioles.
We examined the morphological parameters of arteriolar endothelial and smooth muscle cell dimensions and gap junctional surface areas to obtain an indication of the coupling capacity of each cell type. Silver nitrate staining was utilized to define cell borders of endothelial and smooth muscle cells in arterioles of several vascular beds from two species. From video images of silver-stained arterioles, the mean endothelial cell length of hamster cheek pouch arterioles (diameter 20 to 110 microns) was found to be 141 +/- 2 microns. Mean endothelial cell width was 7 +/- 0.2 microns in the same arterioles. Mean smooth muscle cell length in hamster cheek pouch arterioles of diameter 80 to 150 microns was 66 +/- 3 microns, with an average cell width of 8 +/- 0.2 microns. Dimensions of both endothelial and smooth muscle cells varied moderately with arteriole size and tissue type, but no general trends were seen. Based on the measured dimensions and the specific orientation of cell types within the arteriole, it was calculated that in hamster cheek pouch arterioles (60 microns diameter), 6 or 7 endothelial cell lengths would constitute a 1-mm segment of vessel, whereas approximately 140 smooth muscle cell widths would be required to span the same length. Estimates of connexin43 gap junctional plaque surface areas in each cell type suggest that endothelial cell junctional surface area is approximately eight times that of smooth muscle cells. Thus, combined measurement of cell dimensions and orientation with estimates of junctional plaque density leads to the conclusion that the endothelial cell layer forms a more permissive pathway for longitudinal conduction of signals through the blood vessel.


Brain Metastases of Papillary Thyroid Carcinoma with Horner's Syndrome.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy and has relatively favorable prognosis. Blood-borne metastases of PTC are very rare among the thyroid malignancies. Moreover a case of blood-borne central nervous system metastasized PTC with only unilateral Horner's syndrome, and without any abnormalities in laboratory or physical examinations has not been described before. A 53-year-old female patient had been managed in ophthalmologic clinic due to vague symptoms of right monocular blurred vision with eye dryness for 3 months, but showed no signs of improvement. So it was performed a magnetic resonance imaging and magnetic resonance angiography to evaluate the possibilities of cerebral lesion. And a left frontal mass was incidentally found, and the tumor turned out to be a PTC that had metastasized to brain, regional lymph node, cervical, thoracic spine, and lung. We describe a PTC with extraordinary initial symptoms that metastasized to an unusual site. We recommend that if a papillary thyroid tumor with unusual symptoms or at an advanced stage is found, further investigation should be performed for distant metastasis.


Nociceptin/orphanin FQ slows inspiratory rhythm via its direct effects on the pre-Bötzinger complex.
In a previous study, we showed that in an in vitro en bloc preparation of newborn rats perfused with standard [K(+)] (6.2mM) and high [K(+)] (11.2mM) artificial cerebrospinal fluid (aCSF), nociceptin/orphanin FQ (N/OFQ) suppresses bursting of pre-inspiratory neurons with 1:1 coupling to the fictive inspiration. However, it is unclear whether the pre-Bötzinger complex (preBötC) is involved in the N/OFQ-induced slowing. Using in vitro en bloc preparations with and without the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) perfused with high [K(+)] aCSF, we found the following: (1) there were no differences in the effects of N/OFQ on the inspiratory rhythm between the preparations with and without the RTN/pFRG, (2) N/OFQ decreased the input resistance of inspiratory neurons (Insps) in the preparations without the RTN/pFRG and suppressed their ectopic firing activities, and (3) N/OFQ suppressed the spontaneous firing of Insps under a chemical synaptic transmission blockade. In conclusion, it is possible that the preBötC is involved in N/OFQ-induced inspiratory rhythm slowing.


[Experimental methodologic rationale of the variable results of determining cytosolic estradiol receptors in human breast cancer].
The results of hormonal treatment of mammary tumor patients based on foregoing estradiol receptor investigations are very different by the several authors. In common these results are not enough satisfying. It is tried to show that the dextran-charcoal method widely used in clinical receptor investigations permits a lot of different experimental manipulations which can influence the final result in a deciding manner. To get utilizable results it is an indispensable demand to observe precisely standardized conditions.


A Review of Hand-Arm Vibration Studies Conducted by US NIOSH since 2000.
Studies on hand-transmitted vibration exposure, biodynamic responses, and biological effects were conducted by researchers at the Health Effects Laboratory Division (HELD) of the National Institute for Occupational Safety and Health (NIOSH) during the last 20 years. These studies are systematically reviewed in this report, along with the identification of areas where additional research is needed. The majority of the studies cover the following aspects: (i) the methods and techniques for measuring hand-transmitted vibration exposure; (ii) vibration biodynamics of the hand-arm system and the quantification of vibration exposure; (iii) biological effects of hand-transmitted vibration exposure; (iv) measurements of vibration-induced health effects; (iv) quantification of influencing biomechanical effects; and (v) intervention methods and technologies for controlling hand-transmitted vibration exposure. The major findings of the studies are summarized and discussed.


New types of wheat chromosomal structural variations in derivatives of wheat-rye hybrids.
Chromosomal rearrangements induced by wheat-rye hybridization is a very well investigated research topic. However, the structural alterations of wheat chromosomes in wheat-rye hybrids are seldom reported. Octoploid triticale lines were derived from common wheat Triticum. aestivum L. 'Mianyang11'×rye Secale cereale L. 'Kustro'. Some progeny were obtained by the controlled backcrossing of triticale with 'Mianyang11' and common wheat T. aestivum L. 'Chuannong27' followed by self-fertilization. Fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) using Oligo-pSc119.2-1, Oligo-pTa535-1 and rye genomic DNA as probes were used to analyze the mitotic chromosomes of these progeny. Alterations of wheat chromosomes including 5A, 6A, 1B, 2B, 6B, 7B, 1D, 3D and 7D were observed. 5AL arm carrying intercalary Oligo-pSc119.2-1, Oligo-pTa535-1 or both Oligo-pSc119.2-1 and Oligo-pTa535-1 signals, 6AS, 1BS and 1DL arms containing terminal Oligo-pSc119.2-1 signal, 6BS and 3DS arms without terminal Oligo-pSc119.2-1 signal, 7BS without subtelomeric Oligo-pSc119.2-1 signal and 7DL with intercalary Oligo-pSc119.2-1 signal have been observed. However, these changed wheat chromosomes have not been detected in 'Mianyang11' and Chuannong 27. The altered 5A, 6A, 7B and 7D chromosomes in this study have not been reported and represent several new karyotype structures of common wheat chromosomes. These rearranged wheat chromosomes in the present study afford some new genetic variations for wheat breeding program and are valuable materials for studying the biological function of tandem repetitive DNA sequences.


Estimating relative survival of Italian cancer patients from sparse cancer registries data.
A method is presented for estimating relative survival of cancer patients at the national level from survival data provided by cancer registries covering only a subset of the general population and referring to different, and not necessarily overlapping, incidence periods. Relative survival rates are estimated as a function of the covariates sex, age, epoch of diagnosis, and registry area by means of a multiple regression model. National estimates are then computed by appropriate weighting of the sex-, age-, time- and registry-specific expected relative survival values. The method is illustrated by a sample application to survival data of female breast cancer patients in Italy. The national estimates of breast cancer survival pattern show a mild decrease of survival with age and a marked increase with period of diagnosis.


Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing.
Cardiovascular diseases are a worldwide health problem and are the leading cause of mortality in developed countries. Together with experimental data, the lower incidence of cardiovascular diseases in women than in men of reproductive age points to the influence of sex hormones at the cardiovascular level and suggests that estrogens play a protective role against cardiovascular disease and that this role is also modified by ageing. Estrogens affect cardiovascular function via their specific estrogen receptors to trigger gene expression changes at the transcriptional level. In addition, emerging studies have proposed a role for microRNAs in the vascular effects mediated by estrogens. miRNAs regulate gene expression by repressing translational processes and have been estimated to be involved in the regulation of approximately 30% of all protein-coding genes in mammals. In this review, we highlight the current knowledge of the role of estrogen-sensitive miRNAs, and their influence in regulating vascular ageing.


Toxicity and toxicokinetics of MeISP in isolated rat hepatocytes.
Toxicity and toxicokinetics of a new organophosphorus insecticide, MeISP, in isolated rat hepatocytes were studied. It was found that at the final concentration of 1.5 mmol/L, MeISP can (1) result in an increase of leakage of intracellular enzymes, alanine amino-transferase (ALT), lactate dehydrogenase (LDH), beta-glucuronidase (beta-GDase) and acid phosphatase (AcP) to the medium in a dose-dependent fashion; (2) give rise to obvious plasma membrane blebbing; (3) rapidly deplete the intracellular GSH and (4) almost completely inhibit the protein synthesis and gluconeogenesis from sodium pyruvate. The kinetics study showed that at the final concentration of 15 mumol/L, MeISP is rapidly metabolized and this process fits the one-compartment model. The metabolism of MeISP in the hepatocytes with phenobarbital-induced microsomal enzymes is accelerated. These results indicate that (1) MeISP has obvious toxicity to isolated rat hepatocytes and isolated hepatocytes provide a suitable system to examine the toxic effects of xenobiotics at the cellular level and (2) MeISP is metabolized mainly by microsomal enzymes.


Urban planning and public health at CDC.
Urban planning, also called city and regional planning, is a multidisciplinary field in which professionals work to improve the welfare of persons and communities by creating more convenient, equitable, healthful, efficient, and attractive places now and for the future. The centerpiece of urban planning activities is a "master plan," which can take many forms, including comprehensive plans, neighborhood plans, community action plans, regulatory and incentive strategies, economic development plans, and disaster preparedness plans. Traditionally, these plans include assessing and planning for community needs in some or all of the following areas: transportation, housing, commercial/office buildings, natural resource utilization, environmental protection, and health-care infrastructure. Urban planning and public health share common missions and perspectives. Both aim to improve human well-being, emphasize needs assessment and service delivery, manage complex social systems, focus at the population level, and rely on community-based participatory methods. Both fields focus on the needs of vulnerable populations. Throughout their development, both fields have broadened their perspectives. Initially, public health most often used a biomedical model (examining normal/abnormal functioning of the human organism), and urban planning often relied on a geographic model (analysis of human needs or interactions in a spatial context). However, both fields have expanded their tools and perspectives, in part because of the influence of the other. Urban planning and public health have been intertwined for most of their histories. In 1854, British physician John Snow used geographic mapping of an outbreak of cholera in London to identify a public water pump as the outbreak's source. Geographic analysis is a key planning tool shared by urban planning and public health. In the mid-1800s, planners such as Frederick Law Olmsted bridged the gap between the fields by advancing the concept that community design contributes to physical and mental health; serving as President Lincoln's U.S. Sanitary Commission Secretary; and designing hundreds of places, including New York's Central Park. By 1872, the disciplines were so aligned that two of the seven founders of the American Public Health Association were urban designers (an architect and a housing specialist). In 1926, the U.S. Supreme Court, in validating zoning and land-use law as a legal government authority in Village of Euclid v. Ambler Realty, cited the protection of public health as part of its justification. Other connections have included 1) pioneering urbanist Jane Jacobs, who during the 1960s, called for community design that offered safe and convenient options for walking, biking, and impromptu social interaction; and 2) the Healthy Cities movement, which began in Europe and the United States during the 1980s and now includes projects in approximately 1,000 cities that in various ways highlight the role of health as much more than the presence of medical care.


Magnetic Resonance Imaging-Based Screening for Asymptomatic Brain Tumors: A Review.
Brain tumors comprise 2% of all cancers but are disproportionately responsible for cancer-related deaths. The 5-year survival rate of glioblastoma, the most common form of malignant brain tumor, is only 4.7%, and the overall 5-year survival rate for any brain tumor is 34.4%. In light of the generally poor clinical outcomes associated with these malignancies, there has been interest in the concept of brain tumor screening through magnetic resonance imaging. Here, we will provide a general overview of the screening principles and brain tumor epidemiology, then highlight the major studies examining brain tumor prevalence in asymptomatic populations in order to assess the potential benefits and drawbacks of screening for brain tumors. IMPLICATIONS FOR PRACTICE: Magnetic resonance imaging (MRI) screening in healthy asymptomatic adults can detect both early gliomas and other benign central nervous system abnormalities. Further research is needed to determine whether MRI will improve overall morbidity and mortality for the screened populations and make screening a worthwhile endeavor.


[miR-483-5p aggravates cisplatin-induced premature ovarian insufficiency in rats by targeting FKBP4].
To investigate the role of FKBP4 protein in cisplatin-induced premature ovarian insufficiency (POI). We performed ITRAQ assay of the ovarian tissues from 4 mice with cisplatin-induced POI and 4 control mice, and identified FKBP4 as a significantly down-regulated protein in the oocytes and granulosa cells following cisplatin treatment. TargetScan software was used for target analysis of FKBP4, and qRT-PCR and Western blotting were used to verify the expression levels of miR-483-5p and FKBP4 in the mouse models. Serum samples were collected from patients with POI and healthy women for detecting miR-483-5p level with qRT-PCR. Cell transfection and dual-luciferase assay were performed to determine the relationship between miR-483-5p and FKBP4. In primary granulosa cells and KGN cells, we examined the effect of miR-483-5p alone, miR-483-5p and cisplatin, and miR-483-5p combined with both cisplatin and FKBP4 on cell apoptosis. We also assessed ovarian function in a transgenic mouse model with ovarian miR-483-5p overexpression in comparison wigh wildtype mice using immunofluorescence assay, in situ hybridization and ELISA. Ovarian FKBP4 expression was significantly decreased in mice with cisplatin-induced POI. Analysis using TargetScan software indicated that FKBP4 was the potential target of miR-483-5p, which was highly expressed in the ovaries and serum of POI mice and in the serum of patients with POI. In vitro experiments further confirmed that FKBP4 was the target of miR-483-5p. In KGN and primary granulosa cells, FKBP4 overexpression significantly reduced cell apoptosis induced by both cisplatin and miR-483-5p overexpression (P= 0.0045 and 0.0177, respectively). In the transgenic mice with miR-483-5p overexpression in the oocytes, cisplatin induced more severe ovarian damages as compared with those in the wild-type mice. miR-483-5p/FKBP4 is a new and important pathway in cisplatin-induced POI, in which cisplatin increases ovarian miR- 483-5p expression to result in targeted downregulation of FKBP4. Up-regulation of miR-483-5p may increase ovarian sensitivity to cisplatin and cause severe ovarian dysfunction. Detection of serum miR-483-5p level may help to predict the occurrence and development of POI.


Protozoan enteric infection in AIDS related diarrhea in Thailand.
The aim of this study was to determine the prevalence of enteric protozoa and other pathogens in AIDS patients with diarrhea in Bangkok, Thailand. Of 288 consecutive patients screened in the 10 month period between November 1999-August 2000 inclusive, 55 (19.2%) had Cryptosporidium spp, 13 (4.5%) had Isospora oocyst, 11 (3.8%) had Giardia lamblia, 3 (0.9%) had Entamoeba histolytica, and 1 (0.3%) had Iodamoeba butschlii infection. The prevalence of microsporidia was 11% in this study. Of 251 patients for whom stool culture for bacteria was performed, enteric bacterial pathogens isolated were Campylobacter spp in 18 (7.1%), Salmonella spp in 11 (4.3%), and Shigella spp in 1 (0.5%). Other pathogens found in these patients were Clostridium difficile in 16/102 (15.6%). Mycobacterium spp in 18/287 (6.2%), and Strongyloides stercoralis in 23/288 (8.0%). Overall, parasitic and bacterial pathogens were identified in 140 (48.6%) patients. These pathogens were identified by the routine simple wet smear technique in 32, formalin-ether concentration method in 46, culture for S. stercoralis in 5, and culture for bacteria in 30. Additional test, using modified Ziehl-Neelsen staining, identified cryptosporidial oocyst, isospora oocyst, and Mycobacterium spp in 72. The microsporidia, initially identified by modified trichrome blue staining, all were then determined to be Enterocytozoon bieneusi by thin sectioning electron microscopy. Protozoan and bacterial pathogens were confirmed to be important etiologic agents in diarrhea in AIDS in Thailand. They were all associated with increased mortality. Routine stool examination by simple wet smear detected only one-fourth of these pathogens. Therefore all diagnostic techniques for these organisms should be made more widely available in Thailand.


Prevalence of DSM-IV alcohol diagnoses and symptoms in adolescent community and clinical samples.
Summary prevalence data are critical to determining the utility of DSM-IV criteria for alcohol use disorders among adolescents. This study examined cross-study consistency in the relative prevalence of DSM-IV alcohol symptoms, the ratio of alcohol abuse to dependence diagnoses, the prevalence of the physiological dependence subtype, and the proportion of subthreshold cases of dependence. DSM-IV alcohol diagnosis and symptom prevalence data were obtained from five community and four clinical adolescent samples. There was a moderate level of cross-study agreement on the relative prevalence of alcohol symptoms (mean Spearman p = 0.47). The most common symptoms were dependence criteria: tolerance and drinking more or longer than intended. A relatively high degree of variability in the ratio of abuse to dependence diagnoses and the proportion with physiological dependence was observed. All samples included a significant proportion of subthreshold cases of dependence: up to 12% in community and up to 34% in clinical samples. Alcohol dependence symptoms of tolerance and drinking more or longer than intended have relatively high prevalence among adolescents. These high prevalence symptoms affect the ratio of abuse to dependence diagnoses in some studies, the prevalence of the physiological dependence subtype, and the proportion of subthreshold cases of dependence.


Carnitine and Adiponectin Levels in Breast Cancer after Radiotherapy.
In this study, serum carnitine (CRNT) and adiponectin (APN) levels and the correlation of these parameters in patients with breast cancer before and after treatment with radiotherapy (RT) were determined. Serum adiponectin and carnitine levels were assessed in 58 patients with breast carcinoma and 30 control subjects. Serum carnitine and APN levels were determined using a specific enzyme-linked immunosorbent assay. While serum carnitine level was significantly lower in the patients with breast cancer after RT compared with the control group and before treatment (p=0.002 and p=0.019, respectively), serum APN level was significantly higher than in the control group and before treatment ( p=0.003 and p=0.027, respectively). Carnitine level showed a negative correlation with APN level in the patients after RT (r= -0.626, p= 0.001). There was no correlation between carnitine and APN levels in subjects of control group and before treatment. Also, neither carnitine nor APN levels demonstrated correlation other parameters. Results suggest that increased serum adiponectin and decreased carnitine levels in breast cancer after RT than control group. Carnitine level showed a negative correlation with APN level in the patient with breast cancer after RT. While carnitine, HDL-C and total cholesterol levels are decreased, trygliceride and LDL-C levels are increased in patients than control group. In addition, serum APN concentration was inversely correlated with serum carnitine levels. Furthermore, increased serum APN level in breast cancer after RT might be associated with hypocarnitinemia.


Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions.
Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN. Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the first quarter of 2020 for analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) query was used to identify PN cases. We conducted an initial disproportionality investigation to detect PN adverse event signals associated with the combined use of PI and FXaI by estimating a reporting odds ratio (ROR) with a 95% confidence interval (CI). The adjusted RORs were then analyzed by logistic regression analysis (adjusting for age, gender, and reporting year), and additive/multiplicative models were performed to further confirm the findings. Additionally, subset data analysis was performed on the basis of a single drug of PI and FXaI. Results: A total of 159,317 adverse event reports (including 2,822 PN reports) were included. The combined use of PI and FXaI was associated with a higher reporting of PN (RORadj = 7.890, 95%CI, 5.321-11.698). The result remained significant based on additive/multiplicative methods. The observed association was consistent in the analysis restricted to all specific PI agents (bortezomib and ixazomib) and FXaI (rivaroxaban), except apixaban. Conclusion: Analysis of FAERS data identified reporting associations of PN in the combined use of PI and FXaI, suggesting the need for more robust preclinical and clinical studies to elucidate the relationship.


Multifunctionalized biocompatible microspheres for sensing.
We present our achievements in the synthesis and application of multifunctionalized, cross-linked, polystyrene microspheres, which remarkably and quite generally are taken up by all cell types studied to date. Importantly, the nature of these synthetic beads allows multistep solid-phase chemistry and the ability to bind essentially any molecule/sensor/nucleic acid to them. These microspheres have a number of advantages over other cellular delivery approaches. First, a diverse range of compounds can be attached to the microspheres, and we have demonstrated that these materials are effectively delivered into cells; second, the cellular cargo can be modulated through modification of bead loading; third, they are large enough to be visualized using standard microscopy techniques; and fourth, their cargos are not diluted within the cell. Populations of cells containing beads can be readily sorted from other cells for subsequent analysis with very high, but controllable, uptake rates, which can be modulated through modulation of the bead size and incubation time. Recent work has focused on the development of these microspheres as sensors for intracellular calcium and pH.


Body weight-normalized knee extension strength explains sit-to-stand independence: a validation study.
The purpose of this study was to validate the ability of body weight-normalized knee extension strength to explain sit-to-stand (STS) independence in home care patients. Isometric knee extension force of 31 seated patients (mean age 72.8 years) was measured with a handheld dynamometer. The combined force of both knees was then normalized against body weight. The patients' ability to stand from a chair without using their upper limbs was observed. Independence in the task was correlated significantly (rpb = 0.711, p < 0.001) with strength. Regression analysis revealed a positive odds ratio for strength as a predictor of STS independence (1.197, 1.055-1.357). Receiver operating characteristic analysis showed an area under the curve of 93.7%. The normalized strength cutoff point of 46.3% provided the best sensitivity (85.7%) and specificity (88.2%). This study supports previous research showing a strong relationship between normalized knee extension strength and STS independence. The cutoff points of this and previous studies can serve as goals for muscle strengthening for individuals unable to stand from a chair without use of their upper limbs.


Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?
Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. An overview of BDNF's sensitizing capacity at every level of the pain pathways is presented, including the peripheral nociceptors, dorsal root ganglia, spinal dorsal horn neurons, and brain descending inhibitory and facilitatory pathways. This is followed by the presentation of several potential therapeutic options, ranging from indirect influencing of BDNF levels (using exercise therapy, anti-inflammatory drugs, melatonin, repetitive transcranial magnetic stimulation) to more specific targeting of BDNF's receptors and signaling pathways (blocking the proteinase-activated receptors 2-NK-κβ signaling pathway, administration of phencyclidine for antagonizing NMDA receptors, or blockade of the adenosine A2A receptor). This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.


Fermentation of corn starch to ethanol with genetically engineered yeast.
Expression of the glucoamylase gene from Aspergillus awamori by laboratory and distiller's strains of Saccharomyces cerevisiae allowed them to ferment soluble starch. Approximately 95% of the carbohydrates in the starch were utilized. Glycerol production was significantly decreased when soluble starch was used instead of glucose. Ethanol yield on soluble starch was higher than that on glucose. The rate of starch fermentation was directly related to the level of glucoamylase activity. Strains with higher levels of glucoamylase expression fermented starch faster. The decline in starch fermentation rates toward the end of the fermentation was associated with accumulation of disaccharides and limit dextrins, poor substrates for glucoamylase. The buildup of these products in continuous fermentations inhibited glucoamylase activity and complete utilization of the starch. Under these conditions maltose-fermenting strains had a significant advantage over nonfermenting strains. The synthesis and secretion of glucoamylase showed no deleterious effects on cell growth rates, fermetation rates, and fermentation products.


Large-scale sporting events during the COVID-19 pandemic: insights from the FIFA World Cup 2022 in Qatar with an analysis of patterns of COVID-19 metrics.
The 2022 FIFA World Cup (FIFA-WC) held in Qatar presented unique challenges, given the potential for rapid transmission of coronavirus disease 2019 (COVID-19) among over 1.4 million international fans attending the event. This study aimed to investigate the impact of the FIFA-WC 2022 on COVID-19 cases, deaths, and reproduction rate (R0) in Qatar. Additionally, it sought to understand the implications of hosting large-scale events during a pandemic without COVID-19 restrictive measures, providing critical insights for future decision-making. Data from "Our World in Data" were analysed for three distinct periods: one week before the FIFA-WC (week-preWC), the four weeks of the event (week-1WC to week-4WC), and one week after (week-postWC). The results revealed a significant increase in COVID-19 cases during week-3WC and week-4WC (compared to week-preWC) in Qatar, followed by a subsequent decrease during the week-postWC. Notably, Qatar experienced a more pronounced surge in positive cases than the global trend. Regarding COVID-19-related deaths, Qatar's peak occurred during week-2WC, while globally deaths peaked from week-3WC to week-postWC. Nevertheless, Qatar's death toll remained relatively low compared to the global trend throughout the event. The findings highlight that the FIFA-WC 2022 in Qatar demonstrated the feasibility of organizing large-scale sporting events during a pandemic with appropriate measures in place. They emphasize the importance of high vaccination coverage, continuous monitoring, and effective collaboration between event organizers, healthcare authorities, and governments. As such, the event serves as a valuable model for future gatherings, underlining the significance of evidence-based decision-making and comprehensive public health preparedness.


Dissected aortic sinuses repaired with gelatin-resorcin-formaldehyde (GRF) glue are not stable on follow up.
The chemical glue, gelatin, resorcin and formaldehyde (GRF) is widely used to obliterate the false lumen of acute dissected aortic wall tissue. A retrospective review of 41 consecutive patients operated upon for ascending aortic dissection between 1993 and 2000 was conducted. This study focused on 19 patients with acute aortic dissection in whom the aortic valve was resuspended and GRF glue used in the proximal aortic sinuses. These patients were compared with ascending aortic dissection patients in whom the aortic valve was not resuspended. In total, nine acute and 13 chronic dissections were performed in which aortic valve replacement, valve-sparing root reconstruction (without GRF glue), or no aortic valve surgery was carried out. The operative mortality for ascending aortic dissections was 24.4%; identified risk factors included the specific surgeon involved. Third-degree heart block occurred only in patients in whom GRF glue was used in the proximal aortic sinus (15% incidence). Operative survivors in whom the aortic valve was resuspended and GRF glue used in the proximal aortic sinus, had a 64% incidence of late recurrent aortic regurgitation requiring reoperation due to recurrent aortic sinus aneurysm formation with or without recurrent proximal aortic dissection. No recurrence of aortic regurgitation or proximal disease occurred in the other two groups (p <0.01). Actuarial survival of patients in whom the aortic valve was resuspended with GRF glue was 52.1+/-11.6% at five years and 27.8+/-14.3% at eight years, compared with 55.6+/-16.6% at five years if the aortic valve was not resuspended using GRF glue. The use of GRF glue to repair acute dissected aortic sinuses combined with the resuspension of the aortic valve is associated with an unacceptable incidence of failure of aortic valve repair and recurrence of aortic regurgitation. It may be more appropriate to resect all acute dissected aortic sinus tissue.


The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study.
The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial. We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results. We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy. Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.


Effect of feeding three lysine to energy diets on growth, body composition and age at puberty in replacement gilts.
This study evaluated the effect of diets differing in standard ileal digestible (SID) lysine on lysine intake, growth rate, body composition and age at puberty on maternal line gilts. Crossbred Large White×Landrace gilts (n=641) were fed corn-soybean diets differing in SID lysine concentration (%, g SID lysine:Mcal ME); diets were not isocaloric. Gilts received three grower, finisher diet combinations: low (0.68% lysine grower, 0.52% lysine finisher), medium (0.79% lysine grower, 0.60% lysine finisher) or high (0.90% lysine grower, 0.68% lysine finisher). Grower diets were fed from 100 until 142days of age, and finisher diets were fed until they reached 220days of age. Body weight (BW), backfat thickness (BF), and loin depth (LD) were recorded every 28days. From 160-220days of age, gilts were exposed daily to vasectomized boars and observed for behavioral estrus. Gilts fed the low lysine diet had lower average daily gain and BW (P<0.05), but not fat depth:LD ratio. The percentage of gilts that displayed natural estrus by 220days of age was low but not different among dietary treatments (low 27.7%, medium 31.0% and high 37.7%, respectively; P=0.1201). Gilts fed the high and medium diets reached puberty 10 and 6days earlier, however, than gilts fed the low lysine diet (P<0.05). The rate of puberty attainment may have been less because all gilts contracted porcine epidemic diarrhea (PEDv) just as boar exposure was to begin for the first group of gilts. Results from the present study indicate that growth rate and age at puberty can be altered by ad libitum fed diets that differ in SID lysine concentration.


Quality of Life of the Elderly Receiving Old Age Pension in Lesotho.
The southern African country of Lesotho introduced an old age pension scheme in 2004 with the aim of enhancing the quality of life (QoL) of the nation's elderly population. This study is the first to assess the physical, psychological, social, and environmental aspects of the health-related QoL of the elderly in Lesotho since the pension scheme was adopted. Data for this study were gathered using the World Health Organization QoL-BREF questionnaire. Mean QoL scores were compared across demographic, socioeconomic, and clinical variables using analysis of variance, t test, and regression analysis. Findings indicate that respondents were least satisfied with the environmental and physical domains of QoL. They also indicate that the overall QoL of the elderly in Lesotho was mainly affected by marital status, level of education, type of housing, source of income, and level of satisfaction with income. These factors should thus be taken into account when developing interventions aimed at improving the QoL of the elderly in Lesotho.


Collagen fleece (Tachosil®) for treating testis torsion: A case report.
Testicular torsion is an emergent disease in urology, and there has been discussion of the treatment of testicular torsion. Testicular decompression has been established as a critical treatment for testicular compartment syndrome (TCS), which occurs after detorsion in a patient who is diagnosed with testis torsion. Until now, testicular fasciotomy and incision of tunica albuginea with tunica vaginalis flap (TVF) graft have been suggested for decompression, and some studies about the efficacy of TVF were reported. However, this method is time consuming and needs meticulous technique, so other methods such as orchio-septopexy are suggested. The objective of this clinical case report was to propose new surgical method using collagen fleece (Tachosil®) instead of tunica vagina flap. A 5-year-old boy with scrotal pain visited our hospital 24 h after symptom onset. After history taking, physical examination, and scrotum ultrasonography, he was diagnosed with testis torsion. Emergency surgery was performed after diagnosis. Following the incision of scrotum and fasciotomy, we covered his tunica albuginea with collagen fleece called Tachosil® instead of covering with TVF. Short-term follow-up showed normal blood flow in testis without a TCS. This is the first case report of using Tachosil® in testicular torsion surgery, and its advantages were already reported in other surgeries like Peyronie's disease. Our case suggests this new technique is an appropriate method because of its advantages including its cost-effective and time-saving characteristics. The main limitation is the short follow-up, so more studies are needed to provide a high level of evidence about its efficacy and safety.


Effects of divalent cations on voltage-gated Ca2+ channels and depolarization-induced [Ca2+], transients of freshly isolated pyramidal cells of the rat dorsal cochlear nucleus.
The effects of divalent cations on voltage-activated Ca2+ channels and depolarization-evoked cytoplasmic [Ca2+] elevations were studied in pyramidal neurones isolated from the dorsal cochlear nucleus of the rat. Ca2+ currents were recorded using the whole-cell configuration of the patch-clamp technique. 10 micromol x l(-1) Cd2+ exerted a greater blocking effect on the high-voltage activated (HVA) currents than on the low-voltage activated (LVA) ones (decrease to 26.6+/-2.5% and to 87.8+/-2.1%, respectively). The blocking effect of 200 micromol x l(-1) Cd2+ was more pronounced and the difference between the effect on the HVA and LVA currents became smaller (decrease to 11.7+/-2.1% and to 32.4+/-2.7%, respectively). 200 micromol x l(-1) Ni2+ reduced the LVA component more effectively (to 77.6+/-5.4%) than the HVA one (to 86.9+/-2.6%). Cytoplasmic [Ca2+] changes were measured applying a fluorimetric technique (Fura-2). 10 micromol x l(-1) Cd2+ decreased the peak values of 50 mmol x l(-1) K+ depolarization-induced [Ca2]+i transients to 30.4+/-1.4% while 200 micromol x l(-1) Cd2+ caused a drop to 2.5+/-0.2%. 200 micromol x l(-1) Ni2+ decreased the peak of the transients to 69.6+/-2.9%. Comparison of the blocking effects of divalent cations on Ca2+ currents and [Ca2+]i transients supports further the conclusion that the depolarization-induced [Ca2+]i changes are produced mainly by the activation of the HVA Ca2+ channels.


Crown augmentation using modified bilayered restoration for anchorage: a case report.
An ankylosed tooth can be suitable for obtaining orthodontic anchorage. However, if such a tooth lacks adequate clinical crown height, the anchorage will not be effective. In those situations surgical luxation or restorative crown augmentation is suggested. This case report is about the restorative treatment of an ankylosed, infraoccluded tooth to enhance the anchorage for forced orthodontic eruption of impacted maxillary canines. A crown augmentation in the form of a modified bilayered (sandwich) restoration using GIC, Composite resin and Silver amalgam on left maxillary first molar (26) was successful in sustaining the anchorage for forced eruption and alignment of impacted canines.


Clinical and laboratory studies of nosocomial Staphylococcus aureus resistant to methicillin and aminoglycosides.
A methicillin/aminoglycoside-resistant strain of Staphylococcus aureus (MARS) was likely introduced by transfer of a patient from another hospital. Over the next year, 20 other patients were colonized or infected with MARS of the same phage type, although antibiograms varied. Affected patients usually had serious underlying disease and were in intensive care units. Vancomycin therapy was frequently delayed and MARS may have contributed to the death of some patients. The mode of spread was not definitively delineated, but two nurses were found to be colonized. Institution of isolation procedures was difficult, but the problem gradually waned. Susceptibility testing showed vancomycin to be the most active agent. Synergy studies showed no consistent effect of combining methicillin with an aminoglycoside. This experience illustrates the problem of MARS spread between hospitals and wards, the need for institution of effective control measures, and consideration of early empiric use of vancomycin.